Investigators in Project 1 will focus on the development of vaccine delivery platforms based on nanostructures. The goal is to enhance B cell immunity against HIV-1 gp41 MPER. The specific aims are: Aim 1. To develop a platform for delivering multivalent antigens based on gold nanoparticles. Here, we propose to develop a vaccine platform based on gold nanoparticles (GNP) that will be able to deliver not only multiple copies of antigens, but also immune effector molecules. This platform is relatively simple, but we will be able to control the antigen density, average inter-epitope spacing, and the stoichiomentry of antigens and immune effector molecules. This modular platform is designed to present both the antigen and immune effector molecules to B cells simultaneously to induce maximum antibody response. The platform will be developed using a highly promising gp41-MPER-based antigen we recently developed. Aim 2. To develop a platform for delivering multivalent antigens based on DNA nanostructures. In this Aim, we propose to develop a novel vaccine platform based on 1-D DNA polymer and 2-D DNA lattice that can also deliver multiple copies of antigens as well as immune effector molecules. The major difference between this platform and the one based on GNP is that this one allows more precise control of all of the parameters using programmable, self-assembly of DNA oligonucleotides into a predefined polymer or lattice structure. Although increased sophistication adds some risks, successful completion of this Aim could truly revolutionize the process of formulating vaccines based on short polypeptides. Aim 3. To develop a platform for targeted delivery of antigens encapsulated into nanoparticles. We propose to develop a targeted nanovaccine platform based on biodegradable polyanhydride nanoparticles (BPNs) that can stabilize antigens, provide a depot effect, and serve as an adjuvant. The surface of BPNs will be decorated with carbohydrate moieties that specifically interact with C-type lectins or mannose receptors on dendritic cells and macrophages. The major function of this platform is to enhance helper T cell responses, which in turn will boost B cell response.